Showing papers by "Catholic University of the Sacred Heart published in 2000"

Tracing European founder lineages in the Near Eastern mtDNA pool.

Abstract: Founder analysis is a method for analysis of nonrecombining DNA sequence data, with the aim of identification and dating of migrations into new territory. The method picks out founder sequence types in potential source populations and dates lineage clusters deriving from them in the settlement zone of interest. Here, using mtDNA, we apply the approach to the colonization of Europe, to estimate the proportion of modern lineages whose ancestors arrived during each major phase of settlement. To estimate the Palaeolithic and Neolithic contributions to European mtDNA diversity more accurately than was previously achievable, we have now extended the Near Eastern, European, and northern-Caucasus databases to 1,234, 2,804, and 208 samples, respectively. Both back-migration into the source population and recurrent mutation in the source and derived populations represent major obstacles to this approach. We have developed phylogenetic criteria to take account of both these factors, and we suggest a way to account for multiple dispersals of common sequence types. We conclude that (i) there has been substantial back-migration into the Near East, (ii) the majority of extant mtDNA lineages entered Europe in several waves during the Upper Palaeolithic, (iii) there was a founder effect or bottleneck associated with the Last Glacial Maximum, 20,000 years ago, from which derives the largest fraction of surviving lineages, and (iv) the immigrant Neolithic component is likely to comprise less than one-quarter of the mtDNA pool of modern Europeans.

Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: a randomized trial.

Abstract: ContextNoninvasive ventilation (NIV) has been associated with lower rates of endotracheal intubation in populations of patients with acute respiratory failure.ObjectiveTo compare NIV with standard treatment using supplemental oxygen administration to avoid endotracheal intubation in recipients of solid organ transplantation with acute hypoxemic respiratory failure.Design and SettingProspective randomized study conducted at a 14-bed, general intensive care unit of a university hospital.PatientsOf 238 patients who underwent solid organ transplantation from December 1995 to October 1997, 51 were treated for acute respiratory failure. Of these, 40 were eligible and 20 were randomized to each group.InterventionNoninvasive ventilation vs standard treatment with supplemental oxygen administration.Main Outcome MeasuresThe need for endotracheal intubation and mechanical ventilation at any time during the study, complications not present on admission, duration of ventilatory assistance, length of hospital stay, and intensive care unit mortality.ResultsThe 2 groups were similar at study entry. Within the first hour of treatment, 14 patients (70%) in the NIV group, and 5 patients (25%) in the standard treatment group improved their ratio of the PaO2 to the fraction of inspired oxygen (FIO2). Over time, a sustained improvement in PaO2 to FIO2 was noted in 12 patients (60%) in the NIV group, and in 5 patients (25%) randomized to standard treatment (P = .03). The use of NIV was associated with a significant reduction in the rate of endotracheal intubation (20% vs 70%; P = .002), rate of fatal complications (20% vs 50%; P = .05), length of stay in the intensive care unit by survivors (mean [SD] days, 5.5 [3] vs 9 [4]; P = .03), and intensive care unit mortality (20% vs 50%; P = .05). Hospital mortality did not differ.ConclusionsThese results indicate that transplantation programs should consider NIV in the treatment of selected recipients of transplantation with acute respiratory failure.

Short latency inhibition of human hand motor cortex by somatosensory input from the hand

Abstract: EMG responses evoked in hand muscles by transcranial stimulation over the motor cortex were conditioned by a single motor threshold electrical stimulus to the median nerve at the wrist in a total of ten healthy subjects and in five patients who had electrodes implanted chronically into the cervical epidural space. The median nerve stimulus suppressed responses evoked by transcranial magnetic stimulation (TMS) in relaxed or active muscle. The minimum interval between the stimuli at which this occurred was 19 ms. A similar effect was seen if electrical stimulation was applied to the digital nerves of the first two fingers. Median or digital nerve stimulation could suppress the responses evoked in active muscle by transcranial electrical stimulation over the motor cortex, but the effect was much less than with magnetic stimulation. During contraction without TMS, both types of conditioning stimuli evoked a cutaneomuscular reflex that began with a short period of inhibition. This started about 5 ms after the inhibition of responses evoked by TMS. Recordings in the patients showed that median nerve stimulation reduced the size and number of descending corticospinal volleys evoked by magnetic stimulation. We conclude that mixed or cutaneous input from the hand can suppress the excitability of the motor cortex at short latency. This suppression may contribute to the initial inhibition of the cutaneomuscular reflex. Reduced spinal excitability in this period could account for the mild inhibition of responses to electrical brain stimulation. Several groups have used transcranial magnetic stimulation (TMS) to test how the excitability of the motor cortex is affected by afferent input. Much of the initial work was concerned with testing the concept of excitatory transcortical reflexes. These reflexes are readily obtained in hand muscles after electrical or natural stimulation of cutaneous and/or muscle afferents and have a variety of names, such as LLR II/III, E2, V2, M2 and long-latency stretch reflex (Caccia et al. 1973; Marsden et al. 1976; Jenner & Stephens, 1982; Deuschl et al. 1985). Data from neurological patients very strongly suggests that many of these responses are produced by activity in a transcortical reflex pathway that operates in parallel with spinal systems (Marsden et al. 1977a,b; Jenner & Stephens, 1982; Noth et al. 1985). Experiments with transcranial stimulation gave results that were consistent with this idea. They showed that stimuli capable of eliciting long latency reflexes also increased the excitability of the motor cortex to transcranial magnetic stimulation with a time course consistent with traffic in a transcortical loop (Day et al. 1991). In contrast with these reports, some studies have indicated that peripheral input can suppress the excitability of motor cortex. In a short note, Delwaide & Olivier (1990) reported that stimulation of the median nerve at the wrist could profoundly suppress EMG responses evoked in relaxed hand muscles by transcranial magnetic stimulation of the cortex 18–21 ms later. Similar effects could be seen after stimulation of the cutaneous nerves of the index finger. Since H-reflexes in forearm muscles were unaffected Delwaide & Olivier (1990) suggested that the effect occurred at the cortical rather than the spinal level. Maertens de Noordhout et al. (1992) investigated the sequence of excitatory and inhibitory reflexes (Caccia et al. 1973) in the first dorsal interosseous muscle evoked by electrical stimulation of digital nerves. They used transcranial magnetic and electrical stimulation to show that motor cortical excitability was reduced by electrical stimulation of the digital nerves at a time corresponding to the transition between the initial inhibition and subsequent facilitation of the cutaneomuscular reflex. Palmer & Ashby (1992) reported the same result. Most recently, Bertolasi et al. (1998) found that stimulation of probable muscle afferents in the median nerve could suppress the excitability of cortical projections to forearm extensor muscles whilst radial stimulation suppressed the excitability of cortical projections to forearm flexor muscles. Stimulation of cutaneous afferents in digital nerves failed to have any effect. They suggested that the effect from muscle afferents was a cortical analogue of spinal reciprocal inhibition. The purpose of the present experiments was to extend the original observations of Delwaide & Olivier (1990). They confirm the presence of this early, striking period of inhibition, and show that it is a cortical phenomenon. We also speculate that it is related to and may even be responsible for the initial period of inhibition evident in cutaneo-muscular reflexes of the hand.

Minimum data set for home care: a valid instrument to assess frail older people living in the community.

Abstract: Background.Optimal care for frail elderly patients depends on comprehensive assessment. This is especially true in the complex setting of interdisciplinary home care programs. To facilitate comprehensive assessment, as well as to generate a useful, policy-relevant patient database, standardized, mul

Major Racial Differences in Coronary Constrictor Response Between Japanese and Caucasians With Recent Myocardial Infarction

Abstract: Background—Enhanced coronary vasomotion may contribute to acute coronary occlusion during the acute phase of myocardial infarction (AMI). Japanese have a higher incidence of variant angina than Caucasian patients, but racial differences in vasomotor reactivity early after AMI are controversial. Methods and Results—The same team studied 15 Japanese and 19 Caucasian patients within 14 days of AMI by acetylcholine injection into non–infarct-related (NIRA) and infarct-related (IRA) coronary arteries followed by nitroglycerin. Incidence of vasodilation, vasoconstriction, spasm, and basal tone were assessed in proximal, middle, and distal segments after each drug bolus by quantitative angiography. Japanese patients had much lower cholesterol levels than Caucasians (183±59 versus 247±53 mg/dL, P<0.006) but showed a lower incidence of vasodilation (2% versus 9% of coronary segments) and a greater incidence of spasm after acetylcholine (47% versus 15% of arteries, P<0.00001). Incidence of spasm was higher in IRAs ...

Muscarinic receptor blockade has differential effects on the excitability of intracortical circuits in the human motor cortex

Abstract: The aim of the present study was to investigate whether muscarinic receptor blockade with scopolamine modifies the excitability of specific cortical networks of the human motor cortex as tested with transcranial magnetic stimulation. The effects of scopolamine on the excitability of human motor cortex were investigated in four healthy subjects using transcranial magnetic stimulation before and after an intravenous dose of scopolamine (0.006 mg/kg). We measured the threshold for motor responses, amplitude of motor responses, the duration of the cortical silent period, intracortical inhibition and facilitation, and short-latency inhibition produced by somatosensory input from the hand. In addition, we evaluated the amplitude of motor responses evoked by electrical anodal stimulation, since these responses originate from direct activation of corticospinal axons in the white matter and are not sensitive to changes in cortical excitability. Scopolamine decreased the threshold to magnetic stimuli and increased the amplitude of motor responses evoked by magnetic stimulation. In contrast, motor responses evoked by electrical stimulation were unaffected by administration of scopolamine. Scopolamine also led to a highly significant reduction in the amount of short-latency inhibition produced by somatosensory input from the hand. In contrast, short-latency intracortical inhibition and facilitation were not modified by scopolamine. The differential effect of scopolamine on motor responses evoked by magnetic and electrical stimulation of the motor cortex and the selective effect on somatosensory inhibition demonstrate that muscarinic blockade modifies the excitability of specific cortical networks in the human motor cortex.

Mathematical modelling of the intravenous glucose tolerance test.

Abstract: Several attempts at building a satisfactory model of the glucose-insulin system are recorded in the literature. The minimal model, which is the model currently mostly used in physiological research on the metabolism of glucose, was proposed in the early eighties for the interpretation of the glucose and insulin plasma concentrations following the intravenous glucose tolerance test. It is composed of two parts: the first consists of two differential equations and describes the glucose plasma concentration time-course treating insulin plasma concentration as a known forcing function; the second consists of a single equation and describes the time course of plasma insulin concentration treating glucose plasma concentration as a known forcing function. The two parts are to be separately estimated on the available data. In order to study glucose-insulin homeostasis as a single dynamical system, a unified model would be desirable. To this end, the simple coupling of the original two parts of the minimal model is not appropriate, since it can be shown that, for commonly observed combinations of parameter values, the coupled model would not admit an equilibrium and the concentration of active insulin in the "distant" compartment would be predicted to increase without bounds. For comparison, a simple delay-differential model is introduced, is demonstrated to be globally asymptotically stable around a unique equilibrium point corresponding to the pre-bolus conditions, and is shown to have positive and bounded solutions for all times. The results of fitting the delay-differential model to experimental data from ten healthy volunteers are also shown. It is concluded that a global unified model is both theoretically desirable and practically usable, and that any such model ought to undergo formal analysis to establish its appropriateness and to exclude conflicts with accepted physiological notions.

Infant mortality and congenital anomalies from 1950 to 1994: an international perspective

Abstract: STUDY OBJECTIVE—To provide an international perspective on the impact of congenital anomalies on infant mortality from 1950 to 1994. DESIGN—Population-based study based on data obtained from vital statistics reported to the World Health Organisation. SETTINGS—36 countries from Europe, the Middle East, the Americas, Asia, and the South Pacific. RESULTS—On average, infant mortality declined 68.8 per cent from 1950 to 1994. In the countries studied, infant mortality attributable to congenital anomalies decreased by 33.4 per cent, although it recently increased in some countries in Central and Latin America and in Eastern Europe. Anomalies of the heart and of the central nervous system accounted for 48.9 per cent of infant deaths attributable to congenital anomalies. During 1990-1994, infant mortality attributable to congenital anomalies was inversely correlated to the per capita gross domestic product in the countries studied. At the same time, the proportion of infant deaths attributable to congenital malformations was directly correlated with the per capita gross domestic product. CONCLUSIONS—Congenital malformations account for an increasing proportion of infant deaths in both developed and developing countries. Infant mortality attributable to congenital anomalies is higher in poorer countries although as a proportion of infant deaths it is greater in wealthier countries. Conditions such as spina bifida, whose occurrence can be reduced through preventive strategies, still cause many infant deaths. The apparent increase of infant mortality because of congenital anomalies in some countries should be investigated to confirm the finding, find the causes, and provide prevention opportunities. Keywords: congenital anomalies; infant mortality; spina bifida

ANTIPHOSPHOLIPID ANTIBODIES AFFECT TROPHOBLAST GONADOTROPIN SECRETION AND INVASIVENESS BY BINDING DIRECTLY AND THROUGH ADHERED β2-GLYCOPROTEIN I

Abstract: Antiphospholipid antibodies (aPL) are associated with poor obstetric outcome, such as recurrent abortions, fetal death, growth retardation, and early preeclampsia (1). Passive transfer of whole immunoglobulin fractions from aPL-positive sera has been found to induce fetal loss and growth retardation in pregnant naive mice, suggesting a direct pathogenetic role (2–4). Although it has been assumed that aPL are directed against anionic PL, current advances in the field suggest that antibodies to PL-binding plasma proteins, such as β2-glycoprotein I (β2GPI), can be detected in standard aPL assays (5). Antibodies specific for β2GPI have been identified and found to be associated with the clinical manifestations of the antiphospholipid syndrome (APS) (6–22). The in vivo immunohistologic demonstration of β2GPI on trophoblast surfaces (23,24) and the induction of fetal loss by anti-β2GPI antibodies in experimental animal models (25,26) suggested a role of anti-β2GPI antibodies in fetal loss. Moreover, even murine and human aPL monoclonal antibodies (mAb) specifically reacting with anionic PL in the absence of any plasma cofactor have been shown to produce fetal loss, growth retardation, placental deposition, and necrosis in experimental animal models (3,27,28). Although experimental models have emphasized the role of thrombotic phenomena in placental tissue (4,27), studies in humans have shown that thrombotic events cannot account for all of the histopathologic findings in placentae from women with the APS (29,30). The possibility of direct villous and extravillous trophoblastic damage by aPL through the recognition of phosphatidylserine (PS) exposed during syncytium formation has been suggested (31). Reported direct effects of aPL on trophoblasts have included inhibition of the intercytotrophoblast fusion process (31), of human chorionic gonadotropin (hCG) or placental lactogen secretion (31,32), and/or of trophoblast invasiveness (31). Furthermore, whole IgG fractions from APS patient sera or xenogenic murine anti-PS mAb have been shown to displace annexin V from trophoblasts (and endothelial cell surfaces in the case of human IgG), thus creating conditions favorable to procoagulant state in vitro (31,33). The purpose of the present study was to investigate the in vitro ability of IgG from sera containing high levels of aPL to bind human trophoblast cells and to affect hCG secretion and invasiveness. Furthermore, to identify whether specific effects were related to individual antibody subpopulations, human mAb reacting with β2GPI or with anionic PL in the absence of any plasma cofactor were investigated for their ability to reproduce the binding to trophoblast cell membranes and the modulation of hormone secretion as well as invasiveness. From our results, it appears that trophoblast cells might represent one target for circulating aPL reacting with β2GPI and/or with “pure” anionic PL (whose binding is independent of any plasma cofactor) and that such antibodies affect trophoblast differentiation–related activities.

Clinical effects of a standardized soy extract in postmenopausal women: a pilot study.

Abstract: ObjectiveThis double-blind, randomized study was aimed at evaluating comparatively, in postmenopausal women, the activity of a standardized soy extract (SOYSELECT) and placebo when given alone or in combination with conjugated equine estrogens (CEE) on early climacteric symptoms. Lipid profi

Body mass index and mortality among hospitalized patients

Abstract: Background Body mass index (weight in kilograms divided by the square of the height in meters [BMI]) is known to be associated with overall mortality. However, the effect of age on excess mortality from all causes associated with obesity is controversial. The aim of the present study is to determine the effect of age on the relationship between BMI and mortality. Methods We analyzed data from a large collaborative observational study group, the Italian Group of Pharmacoepidemiology in the Elderly (GIFA), that collected data on hospitalized patients. A total of 18,316 patients consecutively admitted to 79 clinical centers during 5 different surveys in 1998, 1991, 1993, 1995, and 1997 were enrolled in the present study. The main outcome measure was the relative hazard ratio of death for different levels of BMI. Results Mortality rate was lowest among men and women with BMIs from 25.0 through 27.4 kg/m 2 (relative risk, 0.24; 95% confidence interval, 0.15-0.38). The graphed relationship between BMI and mortality in younger patients was hyperbolic, with increased death rates at the lowest and highest BMI rankings. On the contrary, the older patients showed an increased death rate at the lowest BMIs with only a slight elevation at the highest BMIs (>35 kg/m 2 ). Conclusions Our results suggest that BMI, a simple anthropometric measure of nutritional status, is an important predictor of mortality among young and old hospitalized patients. Even when controlling for clinical and functional variables, a low BMI remained a significant and independent predictor of shortened survival. Furthermore, the finding of the high BMI associated with minimum hazard in elderly subjects supports some past findings and opposes others and, if confirmed, has important implications for geriatric clinical guidelines.

Consumption of fresh fruit rich in vitamin C and wheezing symptoms in children

Abstract: BACKGROUND A beneficial effect of fresh fruit consumption on lung function has been observed in several studies. The epidemiological evidence of the effect on respiratory symptoms and asthma is limited. The consumption of fruit rich in vitamin C was examined in relation to wheezing and other respiratory symptoms in cross sectional and follow up studies of Italian children. METHODS Standardised respiratory questionnaires were filled in by parents of 18 737 children aged 6–7 years living in eight areas of Northern and Central Italy. The winter intake of citrus fruit and kiwi fruit by the children was categorised as less than once per week, 1–2 per week, 3–4 per week, and 5–7 per week. A subset of 4104 children from two areas was reinvestigated after one year using a second parental questionnaire to record the occurrence of wheezing symptoms over the intervening period. RESULTS In the cross sectional analysis, after controlling for several confounders (sex, study area, paternal education, household density, maternal smoking, paternal smoking, dampness or mould in the child9s bedroom, parental asthma), intake of citrus fruit or kiwi fruit was a highly significant protective factor for wheeze in the last 12 months (odds ratio (OR) = 0.66, 95% confidence intervals (CI) 0.55 to 0.78, for those eating fruit 5–7 times per week compared with less than once per week), shortness of breath with wheeze (OR = 0.68, 95% CI 0.56 to 0.84), severe wheeze (OR = 0.59, 95% CI 0.40 to 0.85), nocturnal cough (OR = 0.73, 95% CI 0.65 to 0.83), chronic cough (OR = 0.75, 95% CI 0.65 to 0.88), and non-coryzal rhinitis (OR = 0.72, 95% CI 0.63 to 0.83). In the follow up study fruit intake recorded at baseline was a strong and independent predictor of all symptoms investigated except non-coryzal rhinitis. In most cases the protective effect was evident even among children whose intake of fruit was only 1–2 times per week and no clear dose-response relationship was found. The effect was stronger (although not significantly so (p = 0.13)) in subjects with a history of asthma; those eating fresh fruit at least once a week experienced a lower one year occurrence of wheeze (29.3%) than those eating fruit less than once per week (47.1%) (OR = 0.46, 95% CI 0.27 to 0.81). CONCLUSIONS Although the effect of other dietary components cannot be excluded, it is concluded that the consumption of fruit rich in vitamin C, even at a low level of intake, may reduce wheezing symptoms in childhood, especially among already susceptible individuals.

Exhaled 8-isoprostane as a new non-invasive biomarker of oxidative stress in cystic fibrosis.

Abstract: BACKGROUND—Cystic fibrosis is characterised by oxidative stress in the airways. Isoprostanes are prostaglandin isomers formed by free radical catalysed peroxidation of arachidonic acid. 8-Isoprostane is increased in interstitial lung diseases, asthma, chronic obstructive pulmonary disease, and adult respiratory distress syndrome. Exhaled nitric oxide (NO) and carbon monoxide (CO) are biomarkers of inflammation and oxidative stress in the airways, respectively. METHODS—Concentrations of 8-isoprostane in the breath condensate of 10 normal subjects and 19 patients with stable cystic fibrosis were measured using an enzyme immunoassay (EIA). Breath condensate is a non-invasive method of collecting airway secretions. Exhaled nitric oxide (NO) and carbon monoxide (CO) levels were measured by a chemiluminescence analyser. RESULTS—Concentrations of 8-isoprostane in the breath condensate of patients with stable cystic fibrosis were increased about threefold compared with normal subjects (42.7 (4.5) pg/ml vs 15.2 (1.7) pg/ml; p<0.005, 95% CI 14.6 to 40.9). 8-Isoprostane concentrations were negatively correlated with forced expiratory volume in one second in patients with cystic fibrosis (r = −0.61; p<0.005). Exhaled CO was also increased in patients with cystic fibrosis compared with normal subjects (6.7 (1.2) ppm vs 2.9 (0.3) ppm; p<0.05, 95% CI 0.2 to 7.4). 8-Isoprostane concentrations were significantly correlated with CO levels (r = 0.66; p<0.002). CONCLUSIONS—The results of this study show that oxidative stress is increased in cystic fibrosis and may be quantified by measuring 8-isoprostane concentrations in breath condensate.

Phonological grouping is specifically affected in cerebellar patients: a verbal fluency study

Abstract: OBJECTIVES—Recent clinical and functional neuroimaging evidence points towards a cerebellar role in verbal production. At present it is not clear how the cerebellum participates in language production. The aim was to investigate the influence of cerebellar lesions on verbal fluency abilities with specific focus on the verbal searching strategies employed by patients with cerebellar damage. METHODS—Twenty five patients with focal or degenerative cerebellar disease and 14 control subjects were tested in a timed verbal fluency task requiring word production under forced (phonemic or semantic) conditions. To analyse the verbal searching strategy employed, semantic and phonemic cluster analyses were also performed. RESULTS—Performances of cerebellar patients were comparable with those of controls in the semantic task; conversely their performances were significantly impaired when tested in the letter task. Cluster analysis results showed that the verbal fluency impairment is linked to specific damage of phonemically related retrieval strategies. CONCLUSION—Cerebellar damage impairs verbal fluency by specifically affecting phonemic rule performances while sparing semantic rule ones. These findings underline the importance of the cerebellar computing properties in strategy development in the linguistic domain.

The Political Economy of Distress in East Asian Financial Institutions

Abstract: In the East Asian crisis, connections - with industrial groups or influential families - increased the probability of distress for financial institutions. Connections also made closure more, not less, likely, suggesting that the closure processes themselves were transparent. But larger institutions, although more likely to be distressed, were less likely to be closed, suggesting a too big to fail policy. Politics and regulatory capture can play an important role in financial institutions' distress. East Asia's financial crisis featured many distressed and closed financial intermediaries in an environment with many links between government, politicians, supervisors, and financial institutions. This makes the East Asian financial crisis a good event for studying how such connections affect the resolution of financial institutions' distress. Bongini, Claessens, and Ferri investigate distress and closure decisions for 186 banks and 97 nonbank financial institutions in Indonesia, the Republic of Korea, Malaysia, the Philippines, and Thailand. They find that after July 1997, 42 percent of the institutions experienced distress (were closed, merged, or recapitalized, or had their operations temporarily suspended). By July 1999, 13 percent of all institutions in existence in July 1997 had been closed. Using financial data for 1996, the authors find that: Traditional CAMEL-type variables - returns on assets, loan growth, and the ratio of loan loss reserves to capital, of net interest income to total income, and of loans to borrowings - help predict subsequent distress and closure. None of the foreign - controlled institutions was closed, and foreign portfolio ownership lowered an institution`s probability of distress. Connections - with industrial groups or influential families - increased the probability of distress, suggesting that supervisors had granted forbearance from regulations. Connections also made closure more, not less, likely - suggesting that the closure processes themselves were transparent. But larger institutions, although more likely to be distressed, were less likely to be closed, while (smaller) nonbank financial institutions were more likely to be closed. This suggests a too big to fail policy. These policies, together with the fact that resolution processes were late and not necessarily comprehensive, may have added to the overall uncertainty and loss of confidence in the East Asian countries, aggravating the financial crisis. This paper - a product of the Financial Sector Strategy and Policy Group, Financial Sector Vice Presidency - is part of a larger effort in the group to study the causes and resolution of financial distress.

Role of endotoxin and TNF-α in the pathogenesis of experimentally induced coliform mastitis in periparturient cows

Abstract: Twelve cows were experimentally infected in two quarters with 1 × 104 cfu Escherichia coli per quarter and six cows were infused with 500 μg endotoxin into two quarters. Six cows infected intramammarily with Esch. coli were treated intravenously with a bactericidal antibiotic 10 h after infection and subcutaneously 20 h later. Blood and milk samples were collected from all cows at regular time intervals. Milk production decreased more rapidly, but was less pronounced, after endotoxin infusion than during Esch. coli mastitis. The milk production losses in the non-inflamed quarters were negligible in endotoxin mastitis, but were substantial during Esch. coli mastitis, probably due to more pronounced systemic effects. Reticulo-rumen motility was inhibited only during Esch. coli mastitis. Changes in plasma haptoglobin were more pronounced during Esch. coli mastitis, although they occurred sooner during endotoxin mastitis. No changes in plasma activities of enzymes such as lactate dehydrogenase, glutamic–oxaloacetic transaminase and γ-glutamyl transpeptidase were observed. Concentrations of tumour necrosis factor-α increased in both types of mastitis. Absorption of these cytokines into the circulation was highest during Esch. coli mastitis, especially in the untreated control group. We found only minor differences between the treated and untreated Esch. coli groups, but there were larger differences between the Esch. coli groups and the endotoxin group. These differences were probably due to differences in kinetics, composition and amounts of different cytokines released in the mammary gland and subsequently absorption into the circulation. Endotoxin is probably not directly responsible for the systemic changes during coliform mastitis.

Separable processing of consonants and vowels

Abstract: There are two views about the nature of consonants and vowels One view holds that they are categorically distinct objects that play a fundamental role in the construction of syllables in speech production1,2,3 The other view is that they are convenient labels for distinguishing between peak (vowel) and non-peak (consonant) parts of a continuous stream of sound that varies in sonority (roughly the degree of openness of the vocal apparatus during speech)4,5,6, or that they are summary labels for bundles of feature segments7,8 Taking the latter view, consonants and vowels do not have an independent status in language processing Here we provide evidence for the possible categorical distinction between consonants and vowels in the brain We report the performance of two Italian-speaking aphasics who show contrasting, selective difficulties in producing vowels and consonants Their performance in producing individual consonants is independent of the sonority value and feature properties of the consonants This pattern of results suggests that consonants and vowels are processed by distinct neural mechanisms, thereby providing evidence for their independent status in language production

Quercetin inhibits p21-RAS expression in human colon cancer cell lines and in primary colorectal tumors.

Abstract: Immunocytochemical studies have revealed that 10 μM quercetin reduced the steady state levels of p21-ras proteins in both colon cancer cell lines and primary colorectal tumors. These findings were confirmed by Western blot and flow cytometric analysis showing that the inhibition of p21-ras expression by quercetin was time- and concentration-dependent. Twenty-four-hour treatment with 10 μM quercetin reduced p21-ras levels to about 50% of control values. Quercetin was similarly effective in inhibiting the expression of K-, H-, and N-ras proteins. Moreover, the effect of quercetin on ras oncogene expression was not dependent on the cell cycle position of colon cancer cells and appeared to be specific and not merely a consequence of overall inhibition of protein synthesis. Northern blot analysis revealed that quercetin produced in colon cancer cells an early (30 min) reduction of the steady state levels of K-, H-, and N-ras mRNAs. This reduction was also present after 6 hr of flavonoid treatment. These effects of quercetin suggest a possible chemopreventive role for this compound in colorectal carcinogenesis. Int. J. Cancer 85:438–445, 2000. ©2000 Wiley-Liss, Inc.

Acamprosate and relapse prevention in the treatment of alcohol dependence: a placebo-controlled study.

Abstract: The objective of this study was to compare acamprosate with placebo in the treatment of alcohol-dependent patients during a 6-month post-detoxification treatment and a 3-month medication-free follow-up. Patients ( n = 330) were detoxified and randomized to treatment with acamprosate (1998 mg/day) or placebo within an out-patient programme including medical counselling, psychotherapy and self-help groups. The main outcome criterion was drinking behaviour as assessed by: abstinence/relapse ratio, cumulative abstinence duration (CAD) and the period of continued abstinence. Anxiety, depression and craving were also monitored. Intention to treat (ITT) statistical principles were followed. Twenty-five per cent of patients dropped out over the first 6 months. At the end of the treatment period, the abstinence rate was 57.9% for acamprosate and 45.2% for placebo ( P = 0.03). The CAD was 110 ± 77 days for acamprosate and 89 ± 77 days for placebo ( P = 0.016). Patients on acamprosate had a higher continuous abstinence rate and experienced less severe relapses. No differential effect was noted for anxiety, depression or craving. Treatment remained positive, but not significant, 3 months after termination of study medication. No significant difference in adverse events was noted between treatment groups. Acamprosate treatment over 180 days was consistently more effective than placebo to maintain abstinence and to diminish relapse severity.

Patient-reported nonadherence to HAART is related to protease inhibitor levels.

Abstract: Objective To compare self-reported nonadherence with antiretroviral therapy (ART) with predose plasma levels of protease inhibitor (PI). Design A cross-sectional study of consecutive patients from a university-based HIV clinic in Rome, Italy, was conducted. One hundred and forty HIV-infected patients were prescribed regimens containing ritonavir or indinavir. A patient questionnaire assessing knowledge of treatment regimen, adherence behavior, reasons for taking and missing therapy, factors influencing adherence, and health behaviors was administered. A predose PI plasma level was measured concurrently. Results By patient report, 12% missed at least one dose "yesterday," and 24% missed doses in the last 3 days; 14% had a predose plasma concentration below the assay limit of quantitation (2 ritonavir and 18 indinavir samples). Confusion, poor psychological well-being, long office wait, running out of drugs between visits, having relatives to remind the patient to take medication, children, and alteration of sense of taste were related to unquantifiable predose levels of PI. In multivariable analysis, reported nonadherence (odds ratio [OR], 15.8; 95% confidence interval [CI], 4.0-63.3) and confusion (OR, 9.9; 95% CI, 1.4-69.6) were related to unquantifiable predose levels of PI. Conclusion Self-report of missing a dose of antiretroviral medication "yesterday" was related to an unmeasurable plasma PI level.

Biomechanics of the spine.

Abstract: Instability is one of the pathologic conditions of the spine for which surgical treatment is increasingly indicated, even if to-date the definition of instability is controversial. Some aspects of the biomechanics of the spine with particular reference to the viscoelastic characteristics of its elements and the involved loads, are reported. The elasticity of the spine is analyzed with an in-depth consideration of the concept of stability and instability from the biomechanical, clinical and radiographic viewpoint.

Risk of nonmelanoma skin cancer in Italian organ transplant recipients. A registry-based study.

Abstract: BACKGROUND Organ transplant recipients are at an increased risk of nonmelanoma skin cancer. Few data concern heart transplantation and populations from southern Europe. METHODS A total of 1,329 patients who received their first kidney (1,062 subjects) or heart allograft (267 subjects) were included in a partly retrospective cohort study to evaluate the risk of skin cancer. The incidence rate per 1,000 person-years and the cumulative incidence were computed. Standardized morbidity ratio was estimated by comparison with Italian cancer registry data. To analyze the role of potential prognostic factors, Cox's regression method was used. RESULTS The overall incidence rate of nonmelanoma skin cancer was 10.0 cases per 1,000 posttransplant person-years (95% confidence interval 8.2-11.7). This estimate was far higher than expected in the general population. The overall risk of developing skin cancer increased from a cumulative incidence of 5.8% after 5 posttransplant years to an incidence of 10.8% after 10 years of graft survival. In a Cox proportional hazard risk model, the most important factors that appeared to favor the development of skin cancer were age at transplantation and sex. After adjustment for age at transplantation and sex, no definite increased risk was documented among heart as compared with kindney transplant recipients. CONCLUSIONS Our study confirms the increased risk of nonmelanoma skin cancer among organ transplant recipients in a southern European population.